- Email: [email protected]
Non-contact meibography: Keep it simple but effective
Contact Lens & Anterior Eye 35 (2012) 77–80
Contents lists available at SciVerse ScienceDirect
Contact Lens & Anterior Eye journal homepage: www.elsevier.com/locate/clae
Non-contact meibography: Keep it simple but effective H. Pult a,b,∗ , B.H. Riede-Pult a a b
Optometry and Vision Research, Weinheim, Germany Contact Lens & Anterior Eye Research Unit, School of Optometry & Vision Sciences, Cardiff University, UK
a r t i c l e
i n f o
Keywords: Meibomian Gland Dysfunction Meibography Lipid layer Tearfilm stability Dry eye
a b s t r a c t Purpose: Meibography is reported to be important in Meibomian Gland Dysfunction (MGD) evaluation. Our purpose was to investigate the usefulness of a standard infra-red video security camera in meibography. Methods: Meibographs were taken of the right lower lid of 17 subjects (female 10; age = 44.3 years ±13.3 SD), randomly selected from the patient pool of Horst Riede GmbH, Weinheim, Germany. Meibomian glands (MG) were photographed by an near adapted infra-red video security camera and extend of MG loss (MGL) was measured by digital image analyzes. Lipid-layer and non-invasive break-up time (NIBUT) was measured by tearscope, dry eye symptoms were evaluated by the Ocular Surface Disease Index (OSDI). Correlations between MGL scores and ocular signs, tearfilm and symptoms were analyzed by Pearsons, differences between gender by U-test. The ability of MGL to predict dry eye symptoms was evaluated by area under the receiver operative characteristic curve (AUC). Results: MGL scores were significantly correlated to lipid-layer pattern (r = −0.68, p = 0.001) NIBUT (−0.46, 0.032) OSDI (0.89, 0.001) and age (0.61, 0.005). MGL was significantly larger in female (p = 0.001). AUC of MGL was 95.8% (p = 0.001; sensitivity = 88.9%; specificity = 87.5%; threshold = 32.3%). Conclusions: MGL is a predictive test of dry eye symptoms. The analyzed significant correlation between MGL and tearfilm and dry eye symptoms indicates the usefulness of the non-contact IR meibograph (PNCM). © 2011 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
1. Introduction Meibomian Gland Dysfunction (MGD) is one of the most common abnormalities in ophthalmic practice [1] and the major cause of lipid anomaly [2] and therefore of the evaporative dry eye [3]. This was also recognized by the Tearfilm & Ocular Surface Society, which launched the International Workshop on Meibomian Gland Dysfunction (www.tearfilm.org/mgdworkshop/index.html) [3]. According the MGD Workshop, it is recommended to assess MGD by lid morphology, MG mass, gland expressibility, lipid layer and MG drop-out by meibography [3]. Meibography is a technique to visualize the morphology of the MG. There are two different principals: transillumination of the everted lid [4–6] versus direct illumination, named the non-contact meibography [7–10]. In transillumination the lid is everted over a light source [5,11] while non-contact meibography [10] consist of a slit lamp equipped with an infrared charge-coupled device video camera and an infrared transmitting filter [10] to allow the
∗ Corresponding author at: Dr. Heiko Pult - Optometry and Vision Research, Steingasse 15, 69469 Weinheim, Germany. Tel.: +49 6201 477804; fax: +49 6201 873657. E-mail address: [email protected] (H. Pult).
observation of the everted lid without contact to the instrument. To our knowledge, Jester et al. were the first describing meibography by infrared (IR) light [12] and subsequently many other groups used the transillumination IR techniques [4–6,10] in MG observation, but Arita et al. were the first introducing non-contact meibography [7–10]. The latter is commercially available but expensive. The aim of this pilot-study was to analyze if a simple IR security video-camera is useful in meibography instead.
2. Methods Meibographs (Fig. 1) were taken of the lower lid of 17 subjects (female = 10, male = 7; mean age = 44.3 years ±13.3 SD), randomly selected from the patient pool of the Horst Riede GmbH, Weinheim, Germany using a IR CCD video-camera (802CHA CCD; Shenzhen LYD Technology Co. Ltd., Shenzhan, China) which was adapted for near observation by adding a lens system (Figs. 2 and 3). This camera set-up was named the ‘portable non-contact IR meibograph’ (PNCM). Lipid layer and non-invasive tearfilm break-up time (NIBUT) were assessed by the TearScope PlusTM (Keeler Ltd, Windsor, UK). Symptoms were assessed by the Ocular Surface Disease Index (OSDI) and grouped into OSDI− and OSDI+ by a cut-off value of 15 [13,14].
1367-0484/$ – see front matter © 2011 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.clae.2011.08.003
78
H. Pult, B.H. Riede-Pult / Contact Lens & Anterior Eye 35 (2012) 77–80
Fig. 1. Meibographs, taken by the portable non-contact IR meibograph (PNCM). Fig. 4. Computerized analyses of MGL.
Observer was masked against OSDI scores; meibograph analyzes was masked against prior observations. 2.1. Inclusion and exclusion criteria Subjects were excluded if they had diabetes, recent ocular infections, hay fever, any history of ocular surgery, use of any medication or eye drops known to affect the ocular surface, worn contact lenses or had contact lens experiences, or were pregnant. All procedures were conducted in accordance with the Declaration of Helsinki (1983). All subjects gave written informed consent before participating in the study. 2.2. Lipid layer Fig. 2. Sketch of the portable non-contact IR meibograph (PNCM).
Lipid layer was observed using a TearScope PlusTM (Keeler Ltd., Windsor, UK) and classified by lipid pattern appearance according Korb et al. [15]. 2.3. Non-invasive break-up time (NIBUT) NIBUT was measured non-invasively using a TearScope PlusTM with a fine grid insert [16]. NIBUT was the time measured, in seconds, between the full opening of the eyelids after a complete blink and the first break in the tearfilm (using the included stop-watch of the TearScope Plus). Three consecutive readings were evaluated and the median noted. 3. Meibography
Fig. 3. The portable non-contact IR meibograph (PNCM).
An IR CCD video-camera (802CHA CCD; Shenzhen LYD Technology Co. Ltd., Shenzhan, China) was adapted for near observation by adding a lens system (Figs. 2 and 3). The camera was connected to a computer via a Video-to-FireWire Converter DFG/1394-1e (The Image Source Europe GmbH, Bremen, Germany) and photographs were captured by the according software (IC Capture 2.0 and IC Imaging Control 3.1; The Image Source Europe GmbH). Photographs were then analyzed by ImageJ 1.42q (Wayne Rasband, National Institute of Health, USA). The area of MG drop-out was measured and its relation to the total-area calculated (Fig. 4). This factor was named MG loss (MGL).
H. Pult, B.H. Riede-Pult / Contact Lens & Anterior Eye 35 (2012) 77–80
Fig. 5. Relation between MGL and lipid layer thickness.
3.1. Ocular Surface Disease Index (OSDI) Each subject’s symptoms were evaluated after objective observation by a validated German translation of the OSDI questionnaire [17]. Total OSDI scores were calculated as recommended by Schiffman et al. [14]. Subjects were grouped into OSDI− and OSDI+ by a cut-off value of 15 [14]. 4. Statistical analysis Data were tested for normal distribution by the ShapiroWilk test. Correlations between MGL and tearfilm and symptoms were calculated by Pearson correlation, the ability to discriminate between OSDI± was analyzed by the receiver operative characteristic curve (ROC) and area under the ROC (AUC). The data were analyzed using SPSS 16.0 (SPSS Inc., Chicago, USA). 5. Results MGL scores were significantly correlated to lipid-layer pattern (r = −0.68, p = 0.001) (Fig. 5) NIBUT (−0.46, 0.032) (Fig. 6) and age (0.61, 0.005). MGL was significantly larger in female (Utest; p = 0.001). MGL was significantly correlated to OSDI scores (r = 0.89, p = 0.001) (Fig. 7) AUC of MGL was 95.8% (p = 0.001; sensitivity = 88.9%; specificity = 87.5%; threshold = 32.3%) (Fig. 8).
Fig. 6. Relation between MGL and NIBUT.
79
Fig. 7. Relation between MGL and OSDI scores.
6. Discussion Significant correlations between MGL and lipid layer as well as non-invasive break-up time were found. MGD is commonly characterized by qualitative and quantitative changes in the glandular secretion [18]. Consequently a decrease in lipid layer thickness is reasonable in increased MDL. The lipid layer is an important component to stabilize the tearfilm [19]. This is supported by the significant correlation of MGL and non-invasive break-up time, analyzed in this study. However these findings are in accordance to prior investigation using specialized MGD observation techniques [10,11]. These analyzed relations are reasonable and demonstrate that the use of the PNCM gives similar results than published techniques and demonstrate the usefulness of the used IR technique. Many common ophthalmic instruments like topographers do have built-in IR cameras to be designed for pupillometry. We were able to show that these devices can be used in meibography too [20,21]. However slight optical and software modification are recommended [20,21]. Later on this idea was confirmed by Srinivasan et al. [22]. This might make non-contact IR meibography standard practice. A strong relation was found between MGL and OSDI and therefore not surprisingly the MGL showing a good predictive ability of
Fig. 8. Discrimination of the OSDI by MGL.
80
H. Pult, B.H. Riede-Pult / Contact Lens & Anterior Eye 35 (2012) 77–80
dry eye symptoms. A MGL of more than 32% indicate very likely dry eye symptoms. Using the scale of Arita et al. the cut-off value would be a narrow grade 2 (Grade 2 = area loss between one third and two thirds) or using the Nichols scale a narrow grade 3 (Grade 3 = between 25% and 75% partial glands). However, this cut-off value might be missed using these grading scales. Therefore the performed computerized grading of MGL might be an advance method. 7. Conclusions Meibomian gland loss was significantly correlated to tearfilm and dry eye symptoms. MGL seems to be a predictive discriminator between symptomatics and asymptomatics. The portable non-contact IR meibograph (PNCM) is a useful device for meibography. Acknowledgement Presented at the 35th BCLA Conference, Manchester, UK. References [1] Foulks GN, Bron AJ. Meibomian Gland Dysfunction: a clinical scheme for description, diagnosis, classification, and grading. Ocul Surf 2003;1(3):107–26. [2] Knop E, Knop N, Brewitt H, Pleyer U, Rieck P, Seitz B, et al. Meibomian glands: part III Dysfunction - argument for a discrete disease entity and as an important cause of dry eye. Ophthalmologe 2009;106(11):966–79. [3] Nichols KK, Foulks GN, Bron AJ, Glasgow BJ, Dogru M, Tsubota K, et al. The International Workshop on Meibomian Gland Dysfunction: Executive Summary. Invest Ophthalmol Vis Sci 2011;52(4):1922–9. [4] Mathers WD, Daley T, Verdick R. Video imaging of the meibomian gland. Arch Ophthalmol 1994;112(4):448–9. [5] Yokoi N, Komuro A, Yamada H, Maruyama K, Kinoshita S. A newly developed video-meibography system featuring a newly designed probe. Jpn J Ophthalmol 2007;51(1):53–6. [6] Nichols JJ, Berntsen DA, Mitchell GL, Nichols KK. An assessment of grading scales for meibography images. Cornea 2005;24(4):382–8.
[7] Arita R, Itoh K, Maeda S, Maeda K, Furuta A, Tomidokoro A, et al. Proposed diagnostic criteria for seborrheic Meibomian Gland Dysfunction. Cornea 2010;29(9):980–4. [8] Arita R, Itoh K, Maeda S, Maeda K, Tomidokoro A, Amano S. Efficacy of diagnostic criteria for the differential diagnosis between obstructive Meibomian Gland Dysfunction and aqueous deficiency dry eye. Jpn J Ophthalmol 2010;54(5):387–91. [9] Arita R, Itoh K, Inoue K, Kuchiba A, Yamaguchi T, Amano S. Contact lens wear is associated with decrease of meibomian glands. Ophthalmology 2009;116(3):379–84. [10] Arita R, Itoh K, Inoue K, Amano S. Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population. Ophthalmology 2008;115(5):911–5. [11] McCann LC, Tomlinson A, Pearce EI, Diaper C. Tear and meibomian gland function in blepharitis and normals. Eye Contact Lens 2009;35(4):203–8. [12] Jester JV, Rife L, Nii D, Luttrull JK, Wilson L, Smith RE. In vivo biomicroscopy and photography of meibomian glands in a rabbit model of Meibomian Gland Dysfunction. Invest Ophthalmol Vis Sci 1982;22(5):660–7. [13] Pult H, Purslow C, Murphy PJ. The relationship between clinical signs and dry eye symptoms. Eye (Lond) 2011;25(4):502–10. [14] Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol 2000;118(5):615–21. [15] Korb DR, Baron DF, Herman JP, Finnemore VM, Exford JM, Hermosa JL, et al. Tear film lipid layer thickness as a function of blinking. Cornea 1994;13(4):354–9. [16] Guillon JP. Use of the Tearscope Plus and attachments in the routine examination of the marginal dry eye contact lens patient. Adv Exp Med Biol 1998;438:859–67. [17] Michel M, Sickenberger W, Pult H. The effectiveness of questionnaires in the determination of contact lens induced dry eye. Ophthalmic Physiol Opt 2009;29(5):479–86. [18] Nelson JD, Shimazaki J, Benitez-del-Castillo JM, Craig JP, McCulley JP, Den S, et al. The International Workshop on Meibomian Gland Dysfunction: report of the Definition and Classification Subcommittee. Invest Ophthalmol Vis Sci 2011;52(4):1930–7. [19] King-Smith PE, Fink BA, Nichols JJ, Nichols KK, Braun RJ, McFadden GB. The contribution of lipid layer movement to tear film thinning and breakup. Invest Ophthalmol Vis Sci 2009;50(6):2747–56. [20] Pult H, Riede-Pult B. Die meibomschen drüsen, in Optometrie, vol. 11; 2011. Berlin. [21] Pult H, Riede-Pult B. Neues zur meibographie. Die Kontaktlinse 2011;6:24–5. [22] Srinivasan S, Sorbara L, Jones LW, Sickenberger W. Imaging the structure of the meibomian glands. Contact Lens Spectr 2011;7:52–3.
Contents lists available at SciVerse ScienceDirect
Contact Lens & Anterior Eye journal homepage: www.elsevier.com/locate/clae
Non-contact meibography: Keep it simple but effective H. Pult a,b,∗ , B.H. Riede-Pult a a b
Optometry and Vision Research, Weinheim, Germany Contact Lens & Anterior Eye Research Unit, School of Optometry & Vision Sciences, Cardiff University, UK
a r t i c l e
i n f o
Keywords: Meibomian Gland Dysfunction Meibography Lipid layer Tearfilm stability Dry eye
a b s t r a c t Purpose: Meibography is reported to be important in Meibomian Gland Dysfunction (MGD) evaluation. Our purpose was to investigate the usefulness of a standard infra-red video security camera in meibography. Methods: Meibographs were taken of the right lower lid of 17 subjects (female 10; age = 44.3 years ±13.3 SD), randomly selected from the patient pool of Horst Riede GmbH, Weinheim, Germany. Meibomian glands (MG) were photographed by an near adapted infra-red video security camera and extend of MG loss (MGL) was measured by digital image analyzes. Lipid-layer and non-invasive break-up time (NIBUT) was measured by tearscope, dry eye symptoms were evaluated by the Ocular Surface Disease Index (OSDI). Correlations between MGL scores and ocular signs, tearfilm and symptoms were analyzed by Pearsons, differences between gender by U-test. The ability of MGL to predict dry eye symptoms was evaluated by area under the receiver operative characteristic curve (AUC). Results: MGL scores were significantly correlated to lipid-layer pattern (r = −0.68, p = 0.001) NIBUT (−0.46, 0.032) OSDI (0.89, 0.001) and age (0.61, 0.005). MGL was significantly larger in female (p = 0.001). AUC of MGL was 95.8% (p = 0.001; sensitivity = 88.9%; specificity = 87.5%; threshold = 32.3%). Conclusions: MGL is a predictive test of dry eye symptoms. The analyzed significant correlation between MGL and tearfilm and dry eye symptoms indicates the usefulness of the non-contact IR meibograph (PNCM). © 2011 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
1. Introduction Meibomian Gland Dysfunction (MGD) is one of the most common abnormalities in ophthalmic practice [1] and the major cause of lipid anomaly [2] and therefore of the evaporative dry eye [3]. This was also recognized by the Tearfilm & Ocular Surface Society, which launched the International Workshop on Meibomian Gland Dysfunction (www.tearfilm.org/mgdworkshop/index.html) [3]. According the MGD Workshop, it is recommended to assess MGD by lid morphology, MG mass, gland expressibility, lipid layer and MG drop-out by meibography [3]. Meibography is a technique to visualize the morphology of the MG. There are two different principals: transillumination of the everted lid [4–6] versus direct illumination, named the non-contact meibography [7–10]. In transillumination the lid is everted over a light source [5,11] while non-contact meibography [10] consist of a slit lamp equipped with an infrared charge-coupled device video camera and an infrared transmitting filter [10] to allow the
∗ Corresponding author at: Dr. Heiko Pult - Optometry and Vision Research, Steingasse 15, 69469 Weinheim, Germany. Tel.: +49 6201 477804; fax: +49 6201 873657. E-mail address: [email protected] (H. Pult).
observation of the everted lid without contact to the instrument. To our knowledge, Jester et al. were the first describing meibography by infrared (IR) light [12] and subsequently many other groups used the transillumination IR techniques [4–6,10] in MG observation, but Arita et al. were the first introducing non-contact meibography [7–10]. The latter is commercially available but expensive. The aim of this pilot-study was to analyze if a simple IR security video-camera is useful in meibography instead.
2. Methods Meibographs (Fig. 1) were taken of the lower lid of 17 subjects (female = 10, male = 7; mean age = 44.3 years ±13.3 SD), randomly selected from the patient pool of the Horst Riede GmbH, Weinheim, Germany using a IR CCD video-camera (802CHA CCD; Shenzhen LYD Technology Co. Ltd., Shenzhan, China) which was adapted for near observation by adding a lens system (Figs. 2 and 3). This camera set-up was named the ‘portable non-contact IR meibograph’ (PNCM). Lipid layer and non-invasive tearfilm break-up time (NIBUT) were assessed by the TearScope PlusTM (Keeler Ltd, Windsor, UK). Symptoms were assessed by the Ocular Surface Disease Index (OSDI) and grouped into OSDI− and OSDI+ by a cut-off value of 15 [13,14].
1367-0484/$ – see front matter © 2011 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.clae.2011.08.003
78
H. Pult, B.H. Riede-Pult / Contact Lens & Anterior Eye 35 (2012) 77–80
Fig. 1. Meibographs, taken by the portable non-contact IR meibograph (PNCM). Fig. 4. Computerized analyses of MGL.
Observer was masked against OSDI scores; meibograph analyzes was masked against prior observations. 2.1. Inclusion and exclusion criteria Subjects were excluded if they had diabetes, recent ocular infections, hay fever, any history of ocular surgery, use of any medication or eye drops known to affect the ocular surface, worn contact lenses or had contact lens experiences, or were pregnant. All procedures were conducted in accordance with the Declaration of Helsinki (1983). All subjects gave written informed consent before participating in the study. 2.2. Lipid layer Fig. 2. Sketch of the portable non-contact IR meibograph (PNCM).
Lipid layer was observed using a TearScope PlusTM (Keeler Ltd., Windsor, UK) and classified by lipid pattern appearance according Korb et al. [15]. 2.3. Non-invasive break-up time (NIBUT) NIBUT was measured non-invasively using a TearScope PlusTM with a fine grid insert [16]. NIBUT was the time measured, in seconds, between the full opening of the eyelids after a complete blink and the first break in the tearfilm (using the included stop-watch of the TearScope Plus). Three consecutive readings were evaluated and the median noted. 3. Meibography
Fig. 3. The portable non-contact IR meibograph (PNCM).
An IR CCD video-camera (802CHA CCD; Shenzhen LYD Technology Co. Ltd., Shenzhan, China) was adapted for near observation by adding a lens system (Figs. 2 and 3). The camera was connected to a computer via a Video-to-FireWire Converter DFG/1394-1e (The Image Source Europe GmbH, Bremen, Germany) and photographs were captured by the according software (IC Capture 2.0 and IC Imaging Control 3.1; The Image Source Europe GmbH). Photographs were then analyzed by ImageJ 1.42q (Wayne Rasband, National Institute of Health, USA). The area of MG drop-out was measured and its relation to the total-area calculated (Fig. 4). This factor was named MG loss (MGL).
H. Pult, B.H. Riede-Pult / Contact Lens & Anterior Eye 35 (2012) 77–80
Fig. 5. Relation between MGL and lipid layer thickness.
3.1. Ocular Surface Disease Index (OSDI) Each subject’s symptoms were evaluated after objective observation by a validated German translation of the OSDI questionnaire [17]. Total OSDI scores were calculated as recommended by Schiffman et al. [14]. Subjects were grouped into OSDI− and OSDI+ by a cut-off value of 15 [14]. 4. Statistical analysis Data were tested for normal distribution by the ShapiroWilk test. Correlations between MGL and tearfilm and symptoms were calculated by Pearson correlation, the ability to discriminate between OSDI± was analyzed by the receiver operative characteristic curve (ROC) and area under the ROC (AUC). The data were analyzed using SPSS 16.0 (SPSS Inc., Chicago, USA). 5. Results MGL scores were significantly correlated to lipid-layer pattern (r = −0.68, p = 0.001) (Fig. 5) NIBUT (−0.46, 0.032) (Fig. 6) and age (0.61, 0.005). MGL was significantly larger in female (Utest; p = 0.001). MGL was significantly correlated to OSDI scores (r = 0.89, p = 0.001) (Fig. 7) AUC of MGL was 95.8% (p = 0.001; sensitivity = 88.9%; specificity = 87.5%; threshold = 32.3%) (Fig. 8).
Fig. 6. Relation between MGL and NIBUT.
79
Fig. 7. Relation between MGL and OSDI scores.
6. Discussion Significant correlations between MGL and lipid layer as well as non-invasive break-up time were found. MGD is commonly characterized by qualitative and quantitative changes in the glandular secretion [18]. Consequently a decrease in lipid layer thickness is reasonable in increased MDL. The lipid layer is an important component to stabilize the tearfilm [19]. This is supported by the significant correlation of MGL and non-invasive break-up time, analyzed in this study. However these findings are in accordance to prior investigation using specialized MGD observation techniques [10,11]. These analyzed relations are reasonable and demonstrate that the use of the PNCM gives similar results than published techniques and demonstrate the usefulness of the used IR technique. Many common ophthalmic instruments like topographers do have built-in IR cameras to be designed for pupillometry. We were able to show that these devices can be used in meibography too [20,21]. However slight optical and software modification are recommended [20,21]. Later on this idea was confirmed by Srinivasan et al. [22]. This might make non-contact IR meibography standard practice. A strong relation was found between MGL and OSDI and therefore not surprisingly the MGL showing a good predictive ability of
Fig. 8. Discrimination of the OSDI by MGL.
80
H. Pult, B.H. Riede-Pult / Contact Lens & Anterior Eye 35 (2012) 77–80
dry eye symptoms. A MGL of more than 32% indicate very likely dry eye symptoms. Using the scale of Arita et al. the cut-off value would be a narrow grade 2 (Grade 2 = area loss between one third and two thirds) or using the Nichols scale a narrow grade 3 (Grade 3 = between 25% and 75% partial glands). However, this cut-off value might be missed using these grading scales. Therefore the performed computerized grading of MGL might be an advance method. 7. Conclusions Meibomian gland loss was significantly correlated to tearfilm and dry eye symptoms. MGL seems to be a predictive discriminator between symptomatics and asymptomatics. The portable non-contact IR meibograph (PNCM) is a useful device for meibography. Acknowledgement Presented at the 35th BCLA Conference, Manchester, UK. References [1] Foulks GN, Bron AJ. Meibomian Gland Dysfunction: a clinical scheme for description, diagnosis, classification, and grading. Ocul Surf 2003;1(3):107–26. [2] Knop E, Knop N, Brewitt H, Pleyer U, Rieck P, Seitz B, et al. Meibomian glands: part III Dysfunction - argument for a discrete disease entity and as an important cause of dry eye. Ophthalmologe 2009;106(11):966–79. [3] Nichols KK, Foulks GN, Bron AJ, Glasgow BJ, Dogru M, Tsubota K, et al. The International Workshop on Meibomian Gland Dysfunction: Executive Summary. Invest Ophthalmol Vis Sci 2011;52(4):1922–9. [4] Mathers WD, Daley T, Verdick R. Video imaging of the meibomian gland. Arch Ophthalmol 1994;112(4):448–9. [5] Yokoi N, Komuro A, Yamada H, Maruyama K, Kinoshita S. A newly developed video-meibography system featuring a newly designed probe. Jpn J Ophthalmol 2007;51(1):53–6. [6] Nichols JJ, Berntsen DA, Mitchell GL, Nichols KK. An assessment of grading scales for meibography images. Cornea 2005;24(4):382–8.
[7] Arita R, Itoh K, Maeda S, Maeda K, Furuta A, Tomidokoro A, et al. Proposed diagnostic criteria for seborrheic Meibomian Gland Dysfunction. Cornea 2010;29(9):980–4. [8] Arita R, Itoh K, Maeda S, Maeda K, Tomidokoro A, Amano S. Efficacy of diagnostic criteria for the differential diagnosis between obstructive Meibomian Gland Dysfunction and aqueous deficiency dry eye. Jpn J Ophthalmol 2010;54(5):387–91. [9] Arita R, Itoh K, Inoue K, Kuchiba A, Yamaguchi T, Amano S. Contact lens wear is associated with decrease of meibomian glands. Ophthalmology 2009;116(3):379–84. [10] Arita R, Itoh K, Inoue K, Amano S. Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population. Ophthalmology 2008;115(5):911–5. [11] McCann LC, Tomlinson A, Pearce EI, Diaper C. Tear and meibomian gland function in blepharitis and normals. Eye Contact Lens 2009;35(4):203–8. [12] Jester JV, Rife L, Nii D, Luttrull JK, Wilson L, Smith RE. In vivo biomicroscopy and photography of meibomian glands in a rabbit model of Meibomian Gland Dysfunction. Invest Ophthalmol Vis Sci 1982;22(5):660–7. [13] Pult H, Purslow C, Murphy PJ. The relationship between clinical signs and dry eye symptoms. Eye (Lond) 2011;25(4):502–10. [14] Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol 2000;118(5):615–21. [15] Korb DR, Baron DF, Herman JP, Finnemore VM, Exford JM, Hermosa JL, et al. Tear film lipid layer thickness as a function of blinking. Cornea 1994;13(4):354–9. [16] Guillon JP. Use of the Tearscope Plus and attachments in the routine examination of the marginal dry eye contact lens patient. Adv Exp Med Biol 1998;438:859–67. [17] Michel M, Sickenberger W, Pult H. The effectiveness of questionnaires in the determination of contact lens induced dry eye. Ophthalmic Physiol Opt 2009;29(5):479–86. [18] Nelson JD, Shimazaki J, Benitez-del-Castillo JM, Craig JP, McCulley JP, Den S, et al. The International Workshop on Meibomian Gland Dysfunction: report of the Definition and Classification Subcommittee. Invest Ophthalmol Vis Sci 2011;52(4):1930–7. [19] King-Smith PE, Fink BA, Nichols JJ, Nichols KK, Braun RJ, McFadden GB. The contribution of lipid layer movement to tear film thinning and breakup. Invest Ophthalmol Vis Sci 2009;50(6):2747–56. [20] Pult H, Riede-Pult B. Die meibomschen drüsen, in Optometrie, vol. 11; 2011. Berlin. [21] Pult H, Riede-Pult B. Neues zur meibographie. Die Kontaktlinse 2011;6:24–5. [22] Srinivasan S, Sorbara L, Jones LW, Sickenberger W. Imaging the structure of the meibomian glands. Contact Lens Spectr 2011;7:52–3.